You may have come across Siddhartha Mukherjee’s article in the New Yorker on epigenetics, and if so, you may also have noticed that it didn’t make a big hit with biologists who are actually working in the field. Here’s Mark Ptashne giving chapter and verse: the short version is that Mukherjee’s article lets people who don’t know the area (which takes in the vast majority of the people who will read it) come away with a pretty mistaken idea of what epigenetics really is. Particularly upsetting to many biologists was the way the article never even mentioned the phrase “transcription factors”, when the main function of all these epigenetic markers is, in fact, to harness and guide such proteins. The article centers around the differences between Mukherjee’s mother and her identical twin, which is fine as a starting point for discussions of heredity versus environment and how gene expression can be altered by environmental factors. But lay readers could well get the idea that epigenetic markers (such as histone methylation) are some sort of alternate genetic code that transmits information from generation to generation, and that’s not as clear-cut as the article makes it sound. The article certainly raises the possibility, and critics don’t think it does enough to show how contentious the evidence is:
Both Allis and Reinberg understand the implications of transgenerational epigenetic transmission: it would overturn fundamental principles of biology, including our understanding of evolution. Conceptually, a key element of classical Darwinian evolution is that genes do not retain an organism’s experiences in a permanently heritable manner. Jean-Baptiste Lamarck, in the early nineteenth century, had supposed that when an antelope strained its neck to reach a tree its efforts were somehow passed down and its progeny evolved into giraffes. Darwin discredited that model. Giraffes, he proposed, arose through heritable variation and natural selection—a tall-necked specimen appears in an ancestral tree-grazing animal, and, perhaps during a period of famine, this mutant survives and is naturally selected. But, if epigenetic information can be transmitted through sperm and eggs, an organism would seem to have a direct conduit to the heritable features of its progeny. Such a system would act as a wormhole for evolution—a shortcut through the glum cycles of mutation and natural selection.
I should note that Mukherjee has some replies to his critics here, talking with Matthew Herper. From a drug discovery standpoint, epigenetic targets have a lot of appeal because affecting transcription factors directly is brutally hard. So if you can inhibit an enzyme that modifies transcription downstream, you have a handle, because we can generally inhibit enzymes. There is that little problem that we don’t really understand what all these epigenetic enzymes are doing in that great big downstream of gene regulation, but having compounds that affect them is one good way to find out.
Michael Eisen has a good piece on this as well. And he makes a larger point that’s worth keeping in mind, that the word “epigenetics” isn’t just being abused in the wider press. It’s been abused by scientists as well:
But Mukherjee is far from the only one to have fallen into this trap. Which brings me to what I think is the most interesting question here: why does this particular type of epigenetic inheritance involving an obscure biochemical process have such strong appeal? I think there are several things going on.
First, the histone code idea exists (at least for now) in a kind of limbo: enough biochemical specificity to make it clearly real and a ubiquity that makes is seem important, but sufficiently mysterious that people can imbue it with whatever properties they want. And scientists and non-scientists alike have leapt into this molecular biological sweet spot, using the histone code version of epigenetics as a generic explanation for things they can’t understand, a reason to hope that things they want to be true might really be, and as a difficult to refute, almost quasi-religious, argument for the plausibility of almost any idea linked to heredity.
(On Twitter, Jonathan Eisen presented a revised version of this complaint, with the word “epigenetics” crossed out and “the microbiome” substituted as the hand-waving explanation for everything, and he’s got something there, too!) Another good point is that some of this may well be a reaction to all the genetic determinism of the last twenty years or so: it’s written in your genes, you can’t do a thing about it, everything comes down to DNA, etc. That view is in some ways true, but I’ve always liked E. O. Wilson’s photograph analogy (which unfortunately depends on a vanishing technology). He compared a person’s DNA sequence to a photographic negative, which can be printed in all sorts of ways – long and short exposures, dodging, burning, different sorts of paper and developing solutions, etc, to make all kinds of different-looking prints. But at the same time, none of them contain more information than was there in the original negative.
So I think that Eisen is right – any story that can be told about how your DNA really isn’t your destiny is going to get traction, and perhaps more than it deserves. Lamarckian evolution in particular has always been appealing to people, and I think that goes back to a philosophical/religious part of human psychology. (Note in that passage I quoted from Mukherjee that old-fashioned Darwinian mutation and selection is “glum”). Many people would like to think that the good you do will live after you, perhaps actually imprinted on the heredity you pass on to your descendants, and they may also take it as a warning (or as a grim satisfaction) that the sins of the fathers will be visited on the sons. In general, most of us would probably like to see some karma and cosmic justice meted out, and I think that epigenetics is being dragged in as a substitute for religious feelings. Matthew Arnold and Philip Larkin would have understood perfectly.